Disinfectant Rotation

This is the first in a series of quarterly columns authored by Elaine Kopis Sartain. Elaine Kopis Sartain is the Director of the Technical Services Department for the Life Sciences Division of STERIS Corporation, a manufacturer of contamination control and prevention equipment and products. Her primary focus is on microbial control in cleanrooms and other critical environments, and on the selection and validation of CIP cleaning agents.

Elaine provides assistance to STERIS customers in the selection and application of disinfectants and cleaners. She also provides educational seminars and literature to customer groups. Elaine has lectured on microbial control in cleanrooms throughout North America, Europe, and Asia, and has authored numerous published articles on contamination control related topics for industry and professional publications.

Elaine holds a Bachelor of Science degree in Chemistry from Southern Illinois University. She is a member of the Association of Official Analytical Chemists, the American Chemical Society, the Institute of Environmental Sciences and Technology, and the Parenteral Drug Association. Additionally, Elaine is a faculty member of the PDA Training and Research Institute.

I RECENTLY HAD A CONVERSATION with the manufacturing manager for a biotechnology firm who was having problems with recurring microbial excursions in fermentation areas. During the course of our discussion, he informed me that they use a phenolic disinfectant exclusively for one month and then switch to a bleach solution that they also use exclusively for one month. I asked him to explain the rationale for this rotation scheme and he told me that he was not really sure where the rationale originated, but knew that it had been validated.

The obvious question that occurred to me (though I did not ask it) was, “If it’s a validated rotation, then why are you regularly experiencing microbial excursions?” Of course the answer to this may involve more than the facility’s rotation scheme, but the fact that this cleanroom manager could not articulate why he was following this particular disinfectant rotation gave me pause.

I have had, literally, thousands of similar conversations with cleanroom industry customers over the years and have drawn the following conclusions:

There is no universal understanding of why rotation is being done

There is no universal agreement about which chemistries should be rotated

There is no universal agreement about the value of rotation

There is no universal agreement about the optimal frequency of rotation

Why Rotate Disinfectants?
The fundamental purpose of rotation is to prevent selection for resistant organisms; not to prevent organisms from becoming resistant to disinfectants, as is widely believed. Although microorganisms do become resistant on occasion to antibiotic medications, I am not aware of any data demonstrating that microorganisms “become resistant” to disinfectants. These for mulations are simply too toxic and the concentrations are too high, underproper conditions, for resistance to develop.

What actually happens is that either an ineffective chemistry (e.g., alcohol against spore-forming microorganisms) is applied or suboptimal concentrations or contact times are used, so that the expected disinfection performance is not achieved. If one continues with a microbial control program that kills only certain organisms (e.g. vegetative bacteria) while having no impact on others (e.g. spore-formers) then eventually the program does exactly what it has inadvertently been designed to do—select for specific organisms that are inherently resistant to, and cannot be controlled by, the disinfectant technology being applied.

Regulatory Expectations
Though it is not clearly defined by regulatory authorities, the rotation of disinfectants is certainly a regulatory expectation and has been for severalyears. To illustrate, I quote the following guidelines and observations:

From the 483 Observation: “Sanitizing agents (disinfectants) used in the aseptic processing area and the surrounding cleanrooms are not rotated…” (GMP Trends, December 1, 1997).

“The sanitation of clean areas is particularly important. They should be cleaned thoroughly in accordance with a written programme. Where disinfectants are used, more than one type should be employed. Monitoring should be undertaken regularly in order to detect …resistant strains.” (Rules and Guidance for Pharmaceutical Manufacturers and Distributors, {Orange Guide} Annex 1, Section 37, 2002).

“Issues associated with the successful implementation of such a program [cleaning and sanitization] are the development of written procedures, staff training, and decisions on disinfectant rotation…” (USP <1072 > Disinfectants and Antiseptics, In-Process Revision, Pharmacopeial Forum Vol. 29 (3), May-June 2003).

There is little doubt that rotation of disinfectants is required in order to be compliant with US and EU regulatory agencies. In order to be most effective, however, the goal should reach beyond regulatory compliance to achieving improved microbial control through the implementation of a scientifically valid rotation program.

Elements of an Effective Rotation Program
A sound disinfectant rotation program should include chemistries that control a wide variety of organisms and that mitigate damage to cleanroom surfaces. Unfortunately, at this time it is virtually impossible to optimize performance in both of these areas with a single type of chemistry. For this reason,a three-part program should be employed.

1. Routine disinfectants should be used for daily cleaning of non-product contact surfaces and should be able to effectively control vegetative bacteria and remove soil while minimizing damage to cleanroom surfaces and risks to personnel working in the area.

2. In addition, since routine disinfectants will generally not be efficacious against bacterial endospores such as the Bacillus species, a sporicidal agent should also be applied periodically. Since most sporicidal disinfectants are either highly toxic or very corrosive, they should not be considered for daily use.

3. Finally, because both of the above types of chemistry typically leave residues, a residue removal agent (i.e. isopropyl alcohol) should be available and used as needed. An effective rotation program will include all three of these disinfectant types.

Another common rotation scheme that remains a source of debate is the alternation of two similar types of chemistry. The idea behind this type of rotation is to alternate products that have different efficacy profiles. The only reason to support the alternation of two phenol or two quaternary ammonium chloride formulations, however, is if data demonstrates that there is a fundamental formulation-related difference in performance between the two similar products. Likewise, alternating between bleach and oxidizing chemistries such as a hydrogen peroxide or a peracetic acid blend for spore control makes little sense unless there is a fundamental difference in performance that is verifiable.

Another variable that should be considered is the frequency of rotation. If one is alternating between two virtually identical chemistries that offer no distinguishable difference in performance, then the frequency of rotation is a moot point. If, however, one is rotating different chemistries that offer different efficacy profiles, then the rotation frequency should be driven by antimicrobial performance that is verifiable through environmental monitoring data.

As a final general guidance on the subject of disinfectant rotation, I quote again from the USP <1072> In-Process Revision: “It is prudent to augment the daily use of a bactericidal disinfectant with weekly (or monthly) use of a sporicidal agent.” … “Other disinfection rotation schemes may be supported on the basis of review of the historic environmental monitoring data.” Whatever the rationale for its development, any disinfectant rotation program should be able to support ongoing, documented, and thorough antimicrobial efficacy.

A manufacturing manager for a biotech firm told me that they use a phenolic disinfectant exclusively for one month and then switch to a bleach solution for one month. He said he was not really sure where the rationale originated, but knew that it had been validated.

A manufacturing manager for a biotech firm told me that they use a phenolic disinfectant exclusively for one month and then switch to a bleach solution for one month. He said he was not really sure where the rationale originated, but knew that it had been validated.